[go: up one dir, main page]

WO2008157658A1 - Montelukast enrichi en deutérium - Google Patents

Montelukast enrichi en deutérium Download PDF

Info

Publication number
WO2008157658A1
WO2008157658A1 PCT/US2008/067432 US2008067432W WO2008157658A1 WO 2008157658 A1 WO2008157658 A1 WO 2008157658A1 US 2008067432 W US2008067432 W US 2008067432W WO 2008157658 A1 WO2008157658 A1 WO 2008157658A1
Authority
WO
WIPO (PCT)
Prior art keywords
deuterium
abundance
enriched compound
enriched
compound
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/US2008/067432
Other languages
English (en)
Inventor
Anthony Czarnik
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Protia LLC
Original Assignee
Protia LLC
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Protia LLC filed Critical Protia LLC
Publication of WO2008157658A1 publication Critical patent/WO2008157658A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D215/18—Halogen atoms or nitro radicals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents

Definitions

  • This invention relates generally to deuterium-enriched montelukast, pharmaceutical compositions containing the same, and methods of using the same.
  • Montelukast shown below, is a well known leukotriene receptor antagonist.
  • montelukast is a known and useful pharmaceutical, it is desirable to discover novel derivatives thereof. Montelukast is described in U.S. Patent No. 5,565,473; the contents of which are incorporated herein by reference.
  • one object of the present invention is to provide deuterium-enriched montelukast or a pharmaceutically acceptable salt thereof.
  • compositions comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of at least one of the deuterium-enriched compounds of the present invention or a pharmaceutically acceptable salt thereof.
  • Deuterium (D or 2 H) is a stable, non-radioactive isotope of hydrogen and has an atomic weight of 2.0144. Hydrogen naturally occurs as a mixture of the isotopes 1 H (hydrogen or protium), D ( 2 H or deuterium), and T ( 3 H or tritium). The natural abundance of deuterium is 0.015%.
  • the H atom actually represents a mixture of H and D, with about 0.015% being D.
  • compounds with a level of deuterium that has been enriched to be greater than its natural abundance of 0.015% should be considered unnatural and, as a result, novel over their non-enriched counterparts.
  • the hydrogens present on montelukast have different capacities for exchange with deuterium.
  • Hydrogen atoms R1-R2 are easily exchangeable under physiological conditions and, if replaced by deuterium atoms, it is expected that they will readily exchange for protons after administration to a patient.
  • the remaining hydrogen atoms are not easily exchangeable and may be incorporated by the use of deuterated starting materials or intermediates during the construction of montelukast.
  • the present invention is based on increasing the amount of deuterium present in montelukast above its natural abundance. This increasing is called enrichment or deuterium- enrichment. If not specifically noted, the percentage of enrichment refers to the percentage of deuterium present in the compound, mixture of compounds, or composition. Examples of the amount of enrichment include from about 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 16, 21, 25, 29, 33, 37, 42, 46, 50, 54, 58, 63, 67, 71, 75, 79, 84, 88, 92, 96, to about 100 mol%.
  • montelukast Since montelukast has 36 positions, one would roughly expect that for approximately every 240,012 molecules of montelukast (36x6,667), all 36 different, naturally occurring, mono-deuterated montelukasts would be present. This approximation is a rough estimate as it doesn't take into account the different exchange rates of the hydrogen atoms on montelukast. For naturally occurring molecules with more than one deuterium, the numbers become vastly larger. In view of this natural abundance, the present invention, in an embodiment, relates to an amount of an deuterium enriched compound, whereby the enrichment recited will be more than naturally occurring deuterated molecules.
  • the present invention also relates to isolated or purified deuterium-enriched montelukast.
  • the isolated or purified deuterium-enriched montelukast is a group of molecules whose deuterium levels are above the naturally occurring levels (e.g., 3%).
  • the isolated or purified deuterium-enriched montelukast can be obtained by techniques known to those of skill in the art (e.g., see the syntheses described below).
  • the present invention also relates to compositions comprising deuterium-enriched montelukast.
  • the compositions require the presence of deuterium-enriched montelukast which is greater than its natural abundance.
  • the compositions of the present invention can comprise (a) a ⁇ g of a deuterium-enriched montelukast; (b) a mg of a deuterium-enriched montelukast; and, (c) a gram of a deuterium-enriched montelukast.
  • the present invention provides an amount of a novel deuterium- enriched montelukast.
  • amounts include, but are not limited to (a) at least 0.01, 0.02, 0.03, 0.04, 0.05, 0.1, 0.2, 0.3, 0.4, 0.5, to 1 mole, (b) at least 0.1 moles, and (c) at least 1 mole of the compound.
  • the present amounts also cover lab-scale (e.g., gram scale), kilo-lab scale (e.g., kilogram scale), and industrial or commercial scale (e.g., multi-kilogram or above scale) quantities as these will be more useful in the actual manufacture of a pharmaceutical.
  • Industrial/commercial scale refers to the amount of product that would be produced in a batch that was designed for clinical testing, formulation, sale/distribution to the public, etc.
  • the present invention provides a novel, deuterium enriched compound of formula I or a pharmaceutically acceptable salt thereof.
  • R1-R36 are independently selected from H and D; and the abundance of deuterium in R 1 -R 36 is at least 3%.
  • the abundance can also be (a) at least 6%, (b) at least 11%, (c) at least 17%, (d) at least 22%, (e) at least 28%, (f) at least 33%, (g) at least 39%, (h) at least 44%, (i) at least 50%, (j) at least 50%, (k) at least 50%, (1) at least 50%, (m) at least 56%, (n) at least 61%, (o) at least 67%, (p) at least 72%, (q) at least 78%, (r) at least 83%, (s) at least 89%, (t) at least 94%, and (r) 100%.
  • the present invention provides a novel, deuterium enriched compound of formula I or a pharmaceutically acceptable salt thereof, wherein the abundance of deuterium in R1-R2 is at least 50%. The abundance can also be 100%.
  • the present invention provides a novel, deuterium enriched compound of formula I or a pharmaceutically acceptable salt thereof, wherein the abundance of deuterium in R3-R4 is at least 50%. The abundance can also be 100%.
  • the present invention provides a novel, deuterium enriched compound of formula I or a pharmaceutically acceptable salt thereof, wherein the abundance of deuterium in Rs-Rg is at least 25%.
  • the abundance can also be (a) at least 50%, (b) at least 75%, and (c) 100%.
  • the present invention provides a novel, deuterium enriched compound of formula I, wherein the abundance of deuterium in R 9 -R 10 is at least 50%.
  • the abundance can also be 100%.
  • the present invention provides a novel, deuterium enriched compound of formula I or a pharmaceutically acceptable salt thereof, wherein the abundance of deuterium in R 12 -R 15 is at least 25%.
  • the abundance can also be (a) at least 50%, (b) at least 75%, and (c) 100%.
  • the present invention provides a novel, deuterium enriched compound of formula I or a pharmaceutically acceptable salt thereof, wherein the abundance of deuterium in Ri 6 -Ri 9 is at least 25%.
  • the abundance can also be (a) at least 50%, (b) at least 75%, and (c) 100%.
  • the present invention provides a novel, deuterium enriched compound of formula I or a pharmaceutically acceptable salt thereof, wherein the abundance of deuterium in R 20 -R 25 is at least 17%.
  • the abundance can also be (a) at least 33%, (b) at least 50%, (c) at least 67%, (d) at least 83%, and (e) 100%.
  • the present invention provides a novel, deuterium enriched compound of formula I or a pharmaceutically acceptable salt thereof, wherein the abundance of deuterium in R 26 -R 29 is at least 25%.
  • the abundance can also be (a) at least 50%, (b) at least 75%, and (c) 100%.
  • the present invention provides a novel, deuterium enriched compound of formula I or a pharmaceutically acceptable salt thereof, wherein the abundance of deuterium in R30-R31 is at least 50%. The abundance can also be 100%.
  • the present invention provides a novel, deuterium enriched compound of formula I or a pharmaceutically acceptable salt thereof, wherein the abundance of deuterium in R32-R36 is at least 20%.
  • the abundance can also be (a) at least 40%, (b) at least 60%, (c) at least 80%, and (d) 100%.
  • the present invention provides an isolated novel, deuterium enriched compound of formula I or a pharmaceutically acceptable salt thereof.
  • R1-R36 are independently selected from H and D; and the abundance of deuterium in R1-R36 is at least 3%.
  • the abundance can also be (a) at least 6%, (b) at least 11%, (c) at least 17%, (d) at least 22%, (e) at least 28%, (f) at least 33%, (g) at least 39%, (h) at least 44%, (i) at least 50%, (j) at least 50%, (k) at least 50%, (1) at least 50%, (m) at least 56%, (n) at least 61%, (o) at least 67%, (p) at least 72%, (q) at least 78%, (r) at least 83%, (s) at least 89%, (t) at least 94%, and (r) 100%.
  • the present invention provides an isolated novel, deuterium enriched compound of formula I or a pharmaceutically acceptable salt thereof, wherein the abundance of deuterium in R1-R2 is at least 50%. The abundance can also be 100%.
  • the present invention provides an isolated novel, deuterium enriched compound of formula I or a pharmaceutically acceptable salt thereof, wherein the abundance of deuterium in R3-R4 is at least 50%. The abundance can also be 100%.
  • the present invention provides an isolated novel, deuterium enriched compound of formula I or a pharmaceutically acceptable salt thereof, wherein the abundance of deuterium in R5-R8 is at least 25%.
  • the present invention provides an isolated novel, deuterium enriched compound of formula I, wherein the abundance of deuterium in R 9 -R 10 is at least
  • the abundance can also be 100%.
  • the present invention provides an isolated novel, deuterium enriched compound of formula I or a pharmaceutically acceptable salt thereof, wherein the abundance of deuterium in R 12 -R 15 is at 25%.
  • the abundance can also be (a) at least 50%, (b) at least 75%, and (c) 100%.
  • the present invention provides an isolated novel, deuterium enriched compound of formula I or a pharmaceutically acceptable salt thereof, wherein the abundance of deuterium in Ri 6 -Ri 9 is at least 25%.
  • the abundance can also be (a) at least
  • the present invention provides an isolated novel, deuterium enriched compound of formula I or a pharmaceutically acceptable salt thereof, wherein the abundance of deuterium in R 20 -R 25 is at least 17%.
  • the abundance can also be (a) at least
  • the present invention provides an isolated novel, deuterium enriched compound of formula I or a pharmaceutically acceptable salt thereof, wherein the abundance of deuterium in R 26 -R 29 is at least 25%.
  • the abundance can also be (a) at least
  • the present invention provides an isolated novel, deuterium enriched compound of formula I or a pharmaceutically acceptable salt thereof, wherein the abundance of deuterium in R30-R31 is at least 50%. The abundance can also be 100%.
  • the present invention provides an isolated novel, deuterium enriched compound of formula I or a pharmaceutically acceptable salt thereof, wherein the abundance of deuterium in R32-R36 is at least 20%.
  • the abundance can also be (a) at least
  • the present invention provides novel mixture of deuterium enriched compounds of formula I or a pharmaceutically acceptable salt thereof.
  • R1-R36 are independently selected from H and D; and the abundance of deuterium in R1-R36 is at least 3%.
  • the abundance can also be (a) at least 6%, (b) at least 11%, (c) at least 17%, (d) at least 22%, (e) at least 28%, (f) at least 33%, (g) at least 39%, (h) at least 44%, (i) at least 50%, (j) at least 50%, (k) at least 50%, (1) at least 50%, (m) at least 56%, (n) at least 61%, (o) at least 67%, (p) at least 72%, (q) at least 78%, (r) at least 83%, (s) at least 89%, (t) at least 94%, and (r) 100%.
  • the present invention provides a novel mixture of, deuterium enriched compound of formula I or a pharmaceutically acceptable salt thereof, wherein the abundance of deuterium in R1-R2 is at least 50%. The abundance can also be 100%.
  • the present invention provides a novel mixture of, deuterium enriched compound of formula I or a pharmaceutically acceptable salt thereof, wherein the abundance of deuterium in R3-R4 is at least 50%. The abundance can also be 100%.
  • the present invention provides a novel mixture of, deuterium enriched compound of formula I or a pharmaceutically acceptable salt thereof, wherein the abundance of deuterium in R5-R8 is at least 25%.
  • the present invention provides a novel mixture of, deuterium enriched compound of formula I, wherein the abundance of deuterium in R 9 -R 10 is at least
  • the abundance can also be 100%.
  • the present invention provides a novel mixture of, deuterium enriched compound of formula I or a pharmaceutically acceptable salt thereof, wherein the abundance of deuterium in R 12 -R 15 is at least 25%.
  • the abundance can also be (a) at least
  • the present invention provides a novel mixture of, deuterium enriched compound of formula I or a pharmaceutically acceptable salt thereof, wherein the abundance of deuterium in Ri 6 -Ri 9 is at least 25%.
  • the abundance can also be (a) at least
  • the present invention provides a novel mixture of, deuterium enriched compound of formula I or a pharmaceutically acceptable salt thereof, wherein the abundance of deuterium in R 20 -R 25 is at least 17%.
  • the abundance can also be (a) at least
  • the present invention provides a novel mixture of, deuterium enriched compound of formula I or a pharmaceutically acceptable salt thereof, wherein the abundance of deuterium in R 26 -R 29 is at least 25%.
  • the abundance can also be (a) at least
  • the present invention provides a novel mixture of, deuterium enriched compound of formula I or a pharmaceutically acceptable salt thereof, wherein the abundance of deuterium in R30-R31 is at least 50%. The abundance can also be 100%.
  • the present invention provides a novel mixture of, deuterium enriched compound of formula I or a pharmaceutically acceptable salt thereof, wherein the abundance of deuterium in R32-R36 is at least 20%.
  • the abundance can also be (a) at least
  • the present invention provides novel pharmaceutical compositions, comprising: a pharmaceutically acceptable carrier and a therapeutically effective amount of a deuterium-enriched compound of the present invention.
  • the present invention provides a novel method for treating a disease selected from asthma and/or seasonal allergies comprising: administering to a patient in need thereof a therapeutically effective amount of a deuterium-enriched compound of the present invention.
  • the present invention provides an amount of a deuterium- enriched compound of the present invention as described above for use in therapy. [0059] In another embodiment, the present invention provides the use of an amount of a deuterium-enriched compound of the present invention for the manufacture of a medicament (e.g., for the treatment of asthma and/or seasonal allergies).
  • the examples provided in the definitions present in this application are non-inclusive unless otherwise stated. They include but are not limited to the recited examples.
  • the compounds of the present invention may have asymmetric centers. Compounds of the present invention containing an asymmetrically substituted atom may be isolated in optically active or racemic forms. It is well known in the art how to prepare optically active forms, such as by resolution of racemic forms or by synthesis from optically active starting materials. All processes used to prepare compounds of the present invention and intermediates made therein are considered to be part of the present invention. All tautomers of shown or described compounds are also considered to be part of the present invention. [0063] "Host" preferably refers to a human.
  • Treating covers the treatment of a disease-state in a mammal, and includes: (a) preventing the disease-state from occurring in a mammal, in particular, when such mammal is predisposed to the disease-state but has not yet been diagnosed as having it; (b) inhibiting the disease-state, e.g., arresting it development; and/or (c) relieving the disease- state, e.g., causing regression of the disease state until a desired endpoint is reached. Treating also includes the amelioration of a symptom of a disease (e.g., lessen the pain or discomfort), wherein such amelioration may or may not be directly affecting the disease (e.g., cause, transmission, expression, etc.).
  • “Therapeutically effective amount” includes an amount of a compound of the present invention that is effective when administered alone or in combination to treat the desired condition or disorder.
  • “Therapeutically effective amount” includes an amount of the combination of compounds claimed that is effective to treat the desired condition or disorder.
  • the combination of compounds is preferably a synergistic combination. Synergy, as described, for example, by Chou and Talalay, Adv. Enzyme Regul. 1984, 22:27-55, occurs when the effect of the compounds when administered in combination is greater than the additive effect of the compounds when administered alone as a single agent. In general, a synergistic effect is most clearly demonstrated at sub-optimal concentrations of the compounds.
  • “Pharmaceutically acceptable salts” refer to derivatives of the disclosed compounds wherein the parent compound is modified by making acid or base salts thereof.
  • examples of pharmaceutically acceptable salts include, but are not limited to, mineral or organic acid salts of the basic residues.
  • the pharmaceutically acceptable salts include the conventional quaternary ammonium salts of the parent compound formed, for example, from non-toxic inorganic or organic acids.
  • such conventional non-toxic salts include, but are not limited to, those derived from inorganic and organic acids selected from 1, 2- ethanedisulfonic, 2-acetoxybenzoic, 2-hydroxyethanesulfonic, acetic, ascorbic, benzenesulfonic, benzoic, bicarbonic, carbonic, citric, edetic, ethane disulfonic, ethane sulfonic, fumaric, glucoheptonic, gluconic, glutamic, glycolic, glycollyarsanilic, hexylresorcinic, hydrabamic, hydrobromic, hydrochloric, hydroiodide, hydroxymaleic, hydroxynaphthoic, isethionic, lactic, lactobionic, lauryl sulfonic, maleic, malic, mandelic, methanesulfonic, napsylic, nitric, oxalic, pamoic, pantothenic
  • Scheme 1 shows a route to montelukast (Belley, et al, US 4,404,216; Labelle, et al., Bioorg. Med. Chem. Lett. 1995, 5, 283-288; Labelle, Bioorg. Med. Chem. Lett. 1992, 9, 1141- 1146; Graul, Drugs Fut. 1997, 22, 1103).
  • Schemes 2 and 3 show how various deuterated starting materials and intermediates can be used in the chemistry of Scheme 1 to make deuterated montelukast analogs.
  • a person skilled in the art of organic synthesis will recognize that these materials may be used in various combinations to access a variety of other deuterated montelukasts.
  • the aldehyde 1 from Scheme 1 may be made from 9 and 10 according to equation (1) of Scheme 2 (see Suri, et al., WO 2006021974).
  • the known dialdehydes 11 and 12 may be substituted for 10 in this chemistry.
  • Table 1 provides compounds that are representative examples of the present invention.
  • R 1 -R 36 When one of R 1 -R 36 is present, it is selected from H or D.
  • Table 2 provides compounds that are representative examples of the present invention. Where H is shown, it represents naturally abundant hydrogen.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pulmonology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Immunology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne du montelukast enrichi en deutérium, des formes de sel de ce composé pharmaceutiquement acceptables et des procédés de traitement au moyen de ce composé.
PCT/US2008/067432 2007-06-21 2008-06-19 Montelukast enrichi en deutérium Ceased WO2008157658A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US11/766,140 2007-06-21
US11/766,140 US20080319007A1 (en) 2007-06-21 2007-06-21 Deuterium-enriched montelukast

Publications (1)

Publication Number Publication Date
WO2008157658A1 true WO2008157658A1 (fr) 2008-12-24

Family

ID=40137147

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2008/067432 Ceased WO2008157658A1 (fr) 2007-06-21 2008-06-19 Montelukast enrichi en deutérium

Country Status (2)

Country Link
US (1) US20080319007A1 (fr)
WO (1) WO2008157658A1 (fr)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102757311A (zh) * 2012-06-28 2012-10-31 浙江胡涂硅有限公司 一种1，1-环丙二甲醇的制备方法
CN104496899A (zh) * 2015-01-15 2015-04-08 安润医药科技（苏州）有限公司 孟鲁司特钠的中间体的合成方法
CN105085391A (zh) * 2015-06-10 2015-11-25 赖英杰 用作白三烯受体拮抗剂的环丙基不饱和喹啉化合物及应用
CN106928137A (zh) * 2017-02-23 2017-07-07 济南大学 一种石墨烯钯铜催化合成孟鲁斯特钠手性醇中间体的方法

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009018280A2 (fr) * 2007-07-30 2009-02-05 Auspex Pharamaceuticals, Inc. Indoles substitués
WO2014145325A1 (fr) * 2013-03-15 2014-09-18 Protia, Llc Aldéhydes enrichis en deutérium
US9713330B1 (en) 2013-03-15 2017-07-25 Deuteria Agrochemicals, Llc Deuterium-enriched aldehydes
CN112142659A (zh) * 2020-09-07 2020-12-29 宿迁盛基医药科技有限公司 一种孟鲁司特钠中间体的制备方法

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20070082929A1 (en) * 2005-10-06 2007-04-12 Gant Thomas G Inhibitors of the gastric H+, K+-atpase with enhanced therapeutic properties
US20070093467A1 (en) * 2005-10-11 2007-04-26 Chemocentryx, Inc. Piperidine derivatives and methods of use

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5565473A (en) * 1990-10-12 1996-10-15 Merck Frosst Canada, Inc. Unsaturated hydroxyalkylquinoline acids as leukotriene antagonists
US6334997B1 (en) * 1994-03-25 2002-01-01 Isotechnika, Inc. Method of using deuterated calcium channel blockers
CA2396790C (fr) * 2000-01-28 2008-06-17 Ray Cooper Appareil destine a coller un collier de serrage sur un tuyau

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20070082929A1 (en) * 2005-10-06 2007-04-12 Gant Thomas G Inhibitors of the gastric H+, K+-atpase with enhanced therapeutic properties
US20070093467A1 (en) * 2005-10-11 2007-04-26 Chemocentryx, Inc. Piperidine derivatives and methods of use

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102757311A (zh) * 2012-06-28 2012-10-31 浙江胡涂硅有限公司 一种1，1-环丙二甲醇的制备方法
CN104496899A (zh) * 2015-01-15 2015-04-08 安润医药科技（苏州）有限公司 孟鲁司特钠的中间体的合成方法
CN105085391A (zh) * 2015-06-10 2015-11-25 赖英杰 用作白三烯受体拮抗剂的环丙基不饱和喹啉化合物及应用
WO2016197467A1 (fr) * 2015-06-10 2016-12-15 广东默泰同创医药科技有限公司 Composé de quinoléine cyclopropylique insaturée utilisé en tant qu'antagoniste du récepteur des leucotriènes et son utilisation
JP2017521414A (ja) * 2015-06-10 2017-08-03 グァンドン モルテック ファーマ カンパニー リミテッド ロイコトリエン受容体拮抗薬として用いるシクロプロピル不飽和キノリン化合物及びその使用
CN105085391B (zh) * 2015-06-10 2017-08-22 广东默泰同创医药科技有限公司 用作白三烯受体拮抗剂的环丙基不饱和喹啉化合物及应用
US10315997B2 (en) 2015-06-10 2019-06-11 Guangdong Moltech Pharma Co., Ltd. Cyclopropyl unsaturated quinoline compound used as leukotriene receptor antagonist and applications thereof
US10487058B2 (en) 2015-06-10 2019-11-26 Guangdong Moltech Pharma Co. Ltd. Cyclopropyl unsaturated quinoline compound used as leukotriene receptor antagonist and applications thereof
CN106928137A (zh) * 2017-02-23 2017-07-07 济南大学 一种石墨烯钯铜催化合成孟鲁斯特钠手性醇中间体的方法

Also Published As

Publication number Publication date
US20080319007A1 (en) 2008-12-25

Similar Documents

Publication Publication Date Title
US20090082471A1 (en) Deuterium-enriched fingolimod
US20090082366A1 (en) Deuterium-enriched telaprevir
US20090069388A1 (en) Deuterium-enriched sorafenib
WO2008157658A1 (fr) Montelukast enrichi en deutérium
US20090082387A1 (en) Deuterium-enriched nvp-bez234
US20090076056A1 (en) Deuterium-enriched topotecan
US20090076138A1 (en) Deuterium-enriched darunavir
US20090082432A1 (en) Deuterium-enriched ramelteon
US20080299216A1 (en) Deuterium-enriched aripiprazole
US20090076027A1 (en) Deuterium-enriched lurasidone
US20090076167A1 (en) Deuterium-enriched tramiprosate
US20090076036A1 (en) Deuterium-enriched risperidone
US20090076087A1 (en) Deuterium-enriched etoricoxib
US20090062374A1 (en) Deuterium-enriched lasofoxifene
US20090062367A1 (en) Deuterium-enriched eletriptan
WO2008157565A1 (fr) Ézétimibe enrichi en deutérium
US20090082383A1 (en) Deuterium-enriched buprenorphine
WO2008157657A1 (fr) Tenofovir enrichi en deutérium
US20090076117A1 (en) Deuterium-enriched laropiprant
US20090076008A1 (en) Deuterium-enriched fosaprepitant
US20090069295A1 (en) Deuterium-enriched conivaptan
US20090082436A1 (en) Deuterium-enriched rivastigmine
US20090076165A1 (en) Deuterium-enriched memantine
US20090082382A1 (en) Deuterium-enriched naltrexone
US20090082461A1 (en) Deuterium-enriched modafinil

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 08771427

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 08771427

Country of ref document: EP

Kind code of ref document: A1